3.4 | Case Study: D227Y of CD23
CD23 is the low-affinity receptor for IgE. It is expressed in several
hematopoietic cells surface (Acharya et
al., 2010), such as lymphocytes
(Delespesse et al., 1991), monocytes
(Vercelli et al., 1988), follicular
dendritic cells (Krauss, Mayer, Rank, &
Rieber, 1993; Rieber, Rank, Kohler, &
Krauss, 1993), and bone marrow stromal cells
(Fourcade et al., 1992). Several stimuli
regulate the CD23 expression, which is the critical factor for B-cell
activation, growth, and IgE production (OMIM#151445). The D227Y
mutation generated from FCER2 genetic altered had been reported
in head and neck squamous cell carcinoma (HNSCC)
(Stransky et al., 2011) and the
colorectal neuroendocrine carcinomas mutational analyses project
(Woischke et al., 2017). D227 located in
one of the conserved double-loop, which is the interface between CD23
and the carbohydrate protein, Fc\(\varepsilon\)3-4. Moreover,
Ca2+ is a regulated ligand for CD23 binding affinity.
With Ca2+ binding, the loop1 and loop4 would change
the conformation and increase the binding affinity. D227 (loop1) and
D258 (loop4) would form the additional salt bridges between CD23 and
Fc\(\varepsilon\)3-4 (Dhaliwal et al.,
2013; Yuan et al., 2013). Though there
are other bounds involved in CD23 and Fc\(\varepsilon\)3-4 binding, the
D227Y would affect the binding affinity and affect the IgE antitumor
function (Figure 3).
Figure 4 shows the boxplot of the micro-environment descriptors in ASP
altered to TYR sub-group. The distribution of cancer-related SAVs in
several descriptors has a significant difference comparing to the
neutral SAVs, and get a 95% confidence interval by z-test. The
cancer-related SAVs are located in the relatively low packing density
region, whether \(C_{\alpha}\) atoms, nitrogen, or oxygen in a single
SAV chain and whole protein. In the case of D227Y in CD23, it also has
low WCN value in a single SAV chain but has relatively high WCN value in
whole protein or other chains (Figure 4 a, b, and c). It is because D227
is located in the interface of CD23 and Fc\(\varepsilon\)3-4 and is
involved in the binding. Subsequently, the cancer-related SAVs has the
lower distributions of specific tendency of H -neutral (AGPHY),V -small (GASCTPD), V -large(MHKFRYW), Z -low
polarizability(GASDT), Z -high polarizability (KMHFRYW),P -neutral polarity (PATGS), F -basic (HKR),F -nonpolar (AFILMPVW), E -basic (HKR), E -aromatic
(FWY) and E -aliphatic1 (AGP) of neighboring amino acid. This
unique surrounding pattern is also found in the cases D227Y of CD23
(Figure 4 d, e, f, g, h, and i).